OBJECTIVES The main long-term objective of this work is to define the role of ?? T lymphocytes in SIV/HIV infections and utilize this information in our AIDS immunotherapy trials. Our 1998 efforts in this area focused on analyzing the reactivities of ?? T cells against various nonpeptidic ligands. We have developed methods for in vivo sensitization of rhesus macaque (Macaca mulatta) Vgamma9/Vdelta2 T cells. Specifically, intravenous injections of nonpeptidic antigens (DPG) induced an activated state of simian Vgamma9/Vdelta2 T cells which decreased after two months. The activation was detectable with a wide variety of phosphoantigens, such as ribose-1-phosphate (Rib-1-P), xylose-1-phosphate (Xyl-1-P), dimethylallyl-pyrophosphate (DMAPP), monoethyl-pyrophosphate (MEP), diphosphoglyceric acid (DPG), and isopentenyl-pyrophosphate (IPP), or natural (TUBAg-1) phosphoantigens. In parallel experiments, the influence of Vgamma9/Vdelta2 T cells on HIV replication was studied in vitro. The HIV infection of PBMC cultures led to absolute increases in Vgamma9/Vdelta2 T-cell numbers accompanied by decreasing levels of p24. The presence of strong Vgamma9/Vdelta2 T-cell activation resulted in a potent inhibition of HIV replication. Experiments performed in trans-well chambers showed that the in hibitory effect was (at least partially) mediated by soluble factors. Subsequent studies demonstrated that phosphoantigen-activated Vgamma9/Vdelta2 T cells produce substantial amounts of beta-chemokines MIP-1-alpha, MIP-1-beta and RANTES. Time course studies revealed that the beta-chemokine release occurred approximately 4 hours after the in vitro exposure to phosphoantigens. FUTURE DIRECTIONS 1n 1999, we plan to study the effects of in vivo modulations of ?? T-cell activities on the progression of SIV infections. KEY WORDS nonpeptidic antigens, ?? T cells